Activation of Sirt1 decreases adipocyte formation during osteoblast differentiation of mesenchymal stem cells

Cells Tissues Organs. 2009;189(1-4):93-7. doi: 10.1159/000151744. Epub 2008 Aug 28.

Abstract

Mesenchymal stem cells (MSC) can differentiate into osteoblasts, adipocytes, chondrocytes and myoblasts. It has been suggested that a reciprocal relationship exists between the differentiation of MSC into osteoblasts and adipocytes. Peroxisome proliferator-activated receptor gamma2 (PPARgamma2) is a key element for the differentiation into adipocytes. Activation of the nuclear protein deacetylase Sirt1 has recently been shown to decrease adipocyte development from preadipocytes via inhibition of PPARgamma2. In vitro, MSC differentiate to osteoblasts when exposed to bone-inducing medium. However, adipocytes are also developed. In the present study we have targeted Sirt1 to control adipocyte development during differentiation of MSC into osteoblasts. The finding that resveratrol and isonicotinamide markedly inhibited adipocyte and promoted osteoblast differentiation demonstrates an interesting alternative to PPARgamma antagonists. These results are important for the evolving field of cell-based tissue engineering, but may also be relevant in the search for new treatments of osteoporosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology*
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Animals
  • Biomarkers / metabolism
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Calcitriol / pharmacology
  • Cell Differentiation / drug effects*
  • Cell Line
  • Gene Expression Regulation / drug effects
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Osteoblasts / cytology*
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Rats
  • Sirtuin 1
  • Sirtuins / metabolism*
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism

Substances

  • Biomarkers
  • Sirt1 protein, mouse
  • Sirtuin 1
  • Sirtuins
  • Calcitriol